To further its efforts to balance risks and benefits with respect to approving medical devices through the premarket approval (PMA) pathway or utilizing the de novo classification process, FDA has now issued a draft guidance, "Factors to Consider When Making Benefit-Risk Determinations for Medical Device Investigational Device Exemptions (IDEs)" (Draft Guidance). FDA states that a primary purpose of the draft guidance is “to clarify the factors that FDA considers when assessing risks and anticipated benefits for approving IDE studies, and how uncertainty may be offset by a variety of risk mitigation measures which can assure appropriate patient and research participant protections in investigational research settings.” Draft Guidance, at 5 (emphasis in original).

The draft guidance states three considerations made by FDA in assessing the benefit-risk of an IDE: 1) the stage of development of the device, 2) the maturity of the proposed technology, and 3) the availability of non-clinical testing to complement or replace the need for clinical testing.

FDA acknowledges that “device investigations during different stages of development are generally associated with different types of risk, and different levels of uncertainty.” Draft Guidance, at 12. For example, “a greater degree of uncertainty is expected for novel technologies, and at earlier stages of device development, such as first in human or early feasibility trials, while relatively more certainty is expected in traditional feasibility and pivotal trials.” Id. The benefit-risk assessment “should focus on whether a proposed study is well-designed to meet its stated objectives as appropriate to the stage of development for the investigated device.” Id.

FDA also recognized the importance of non-clinical data in potentially obviating or reducing the need for additional clinical testing “to evaluate certain aspects of device design or performance.” Id.

As with its guidance on benefit-risk determinations for PMAs and de novo submission, the IDE draft guidance addresses the role of patient preference in weighing risks and benefits. The Draft Guidance notes that patients may consider various risks and benefits in a manner different from their family or physician, and also that some patients may be willing to take on higher risks to achieve a small benefit, while others are risk averse. FDA says it intends to evaluate these different factors in its review of IDE submissions.

An important part of assessing the benefits and risks are the mitigations put in place to manage the risks. Such measures may include building safety features into the device, use of protective measures, and communication of safety information. The Draft Guidance notes that “the preferred hierarchy of risk mitigation is to first attempt to eliminate the risk, then if this is not possible, to design and implement protective measures, and communicate the residual risk to patients and operators such as by labeling.” Draft Guidance, at 20.

The Draft Guidance describes FDA’s assessment of the benefits to the study subjects as well as to others. Key elements include the type of benefit, magnitude of the benefit, probability of the participant experiencing one or more benefits, and duration of the effect. FDA will also consider the extent to which the “study will yield generalizable knowledge about the disorder or condition being studied.” Draft Guidance, at 22.

Similar to the benefit-risk considerations for PMAs and de novo classifications, FDA also says it will consider the following: characterization of the disease, availability of alternatives, subject tolerance for risk and perspective on benefit, uncertainty, and least burdensome study design.

The Draft Guidance concludes with an appendix that describes the benefit-risk information that an IDE sponsor should include in its submission. A second appendix provides hypothetical examples of summary benefit-risk assessments. It is encouraging that FDA continues to focus on the balance between benefits and risks, recognizes that pre-clinical data can reduce clinical requirements, and recognizes that there may be different considerations for different patient populations.